Glucocorticoid-induced hypertension: from mouse to man

Area of Science:

• Endocrinology
• Cardiovascular Physiology
• Hypertension Research

Background:

• Adrenocorticotrophic hormone (ACTH) is known to elevate blood pressure across multiple species.
• In rats and humans, ACTH-induced hypertension is primarily mediated by glucocorticoid excess, unlike in sheep.
• Glucocorticoid excess impacts cardiovascular function, leading to elevated blood pressure.

Purpose of the Study:

• To investigate the mechanisms underlying ACTH-induced hypertension in rats and humans.
• To explore the role of the nitric oxide system in glucocorticoid-mediated hypertension.
• To assess the efficacy of classical receptor blockers in preventing glucocorticoid hypertension.

Main Methods:

• Comparative analysis of blood pressure regulation in response to ACTH administration.
• Measurement of cardiac output and renal vascular resistance.
• Investigation of the nitric oxide system's involvement.
• Pharmacological blockade of glucocorticoid and mineralocorticoid receptors.

Main Results:

• ACTH increases blood pressure in humans, rats, and mice.
• Hypertension in rats and humans is associated with increased cardiac output and renal vascular resistance.
• The nitric oxide system plays a role in glucocorticoid hypertension in both species.
• Classical glucocorticoid and mineralocorticoid receptor blockers do not prevent hypertension from naturally occurring glucocorticoids.

Conclusions:

• Glucocorticoid excess is a key factor in ACTH-induced hypertension in rats and humans.
• The nitric oxide pathway is implicated in the development of glucocorticoid hypertension.
• Abnormalities in glucocorticoid metabolism may be a contributing factor to essential hypertension.